Gene Therapy

Spark’s delivery vector triggers another troubling immune reaction, but R&D team maintains hemophilia B efficacy

Katherine A. High, Spark

Katherine A. High, Spark

One month after Spark Therapeutics $ONCE spooked its investors with the news of one immune reaction to its gene therapy in a small hemophilia B study, its investigators turned up at ASH to add one more case to concern its backers. But the biotech wasn’t unprepared, coming back with evidence that they were still able to control the immune reaction to SPK-9001 while all but one of 9 patients clearly remained free of bleeds.

An immune reaction is one thing you never want to see after delivering a gene therapy, which uses inactivated viruses to try and safely deliver a gene fix for a particular genetic malfunction. But the spike in liver enzymes flagged an immune response to the Spark100 delivery vehicle for two patients. Factor IX activity — the protein needed for blood to clot — dropped from 32% to 12% in one of those patients, but stayed at a therapeutic level.

Researchers put that patient on a tapering course of corticosteroids. The other immune response was dealt with more quickly with steroids, and the Factor IX peak activity slipped from 71% to 68%.

One of the 9 needed an infusion to control a suspected knee bleed even though the participant has a Factor IX level of 36%.

This time around Spark, which is partnered with pharma giant Pfizer $PFE, was ready to start reassuring observers, even though it had more bad news to deliver.

“We will monitor these two participants carefully as we continue to taper the corticosteroids,” said Katherine A. High, M.D., president and chief scientific officer at Spark Therapeutics, in a statement. “It’s important to remember that the immune response to the capsid typically is transient, and in both cases, seems to have been arrested by corticosteroids. Once corticosteroids have been discontinued altogether, levels of expression will be the best measure of the efficacy of this approach. The experience we have gained in immuno-monitoring and in clinical management of the immune response in the hemophilia B trial will further inform our upcoming hemophilia studies.”


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RAPS Regulatory Convergence 2017